Table 18: Diagnostic work up of neonates with ambiguous genitalia

Good history (family, maternal, neonatal)

Parental consanguinity

Previous intersex disorders or genital anomalies

Previous neonatal deaths

Primary amenorrhoea or infertility in other family members

Maternal exposure to androgens

Failure to thrive, vomiting, diarrhoea of the neonate Physical examination

Pigmentation of genital and areolar area

Hypospadias or sinus urogenitalis

Size of phallus

Palpable and/or symmetrical gonads

Blood pressure Investigations

Buccal smear

Blood: 17-hydroxyprogesterone, electrolytes, LH, FSH, TST, Cortisol, ACTH

Urine: adrenal steroids

Karyotype

Ultrasound

Genitogram

HCG stimulation test

Androgen binding studies

Endoscopy

LH = luteinizing hormone; FSH = follicle stimulating hormone; TST = testosterone; HCG = human chorionic gonadotrophin ACTH = adrenocortico tropic hormone

It must be remembered that if one can feel a gonad it is almost certainly a testis, therefore this clinical finding virtually excludes female pseudohermaphrodites (i.e. САН). The following laboratory investigations are mandatory:

• Buccal smear (if available with accuracy)

• Plasma 17-OH-progesteron assay

• Plasma electrolytes

These investigations will give evidence of САН, which is the most frequent intersex disorder, and if this is the case no further investigation is needed. Otherwise the laboratory work up proceeds accordingly. The HCG stimulation test is particularly helpful in differentiating the main syndromes of male pseudohermaphrodites and in evaluating Leydig cell potential and phallic growth potential.

HCG stimulation test in male pseudohermaphrodites:

• Normal increase in both TST and DHTST = androgen insensitivity syndrome

• Subnormal increase in both TST and DHTST with increasing androgen precursors = TST biosynthetic
block

• Normal increase in TST but subnormal increase in DHTST = 5a reductase deficiency.

The following rules of thumb can be applied regarding a precise diagnosis:

• Positive buccal smear test and no palpable gonads is САН or female pseudohermaphrodite due to
maternal exposure to androgens. In the case of САН, immediate medical therapy must be instituted
(corticosteroid substitution, electrolyte and blood pressure monitoring).

• Negative buccal smear test and one or two gonads palpable (more often inguinal) - if there are Mullerian
duct structures, then the anomaly concerns gonadal dysgenesis or true hermaphroditism; if there are no
Mullerian duct structures, the anomaly concerns a male hermaphrodite due either to abnormal TST
biosynthesis, inadequate conversion of TST to DHTST (5a-reductase deficiency) or receptor anomaly
(androgen insensitivity syndrome)

The decision for appropriate sex assignment is taken on account of a precise aetiological diagnosis and the functional potential of the genitalia. Schematically this practical outline can be applied:

• Female pseudohermaphrodites (i.e. САН) should be reared as female since genitoplasty can correct
virilization, and spontaneous puberty, sexual intercourse and fertility are to be expected.

• Male pseudohermaphrodites with an inadequate phallus should be given androgenotherapy, i.e. TST,
and those with a poor clinical response should be reared as girls. The only exception is 5a-reductase
deficiency patients, if recognized, in whom a masculine puberty is expected and may be reared as
male.

• True hermaphrodites are preferably reared as girls as they have adequate Mullerian structures, i.e.
vagina.

• Mixed gonadal dysgenesis patients with inadequate phallus and intra-abdominal testis are preferably
reared as girls. Male sex may, however, be chosen when the phallus has adequate size and cavernosum
and the testis is palpable, inguinal or scrotal,

• Pure gonadal dysgenesis patients are reared as girls.